Procalcitonin (PCT) has become a well-established biomarker for the diagnosis of sepsis. PCT reflects the severity of a bacterial infection and is in particular used to monitor progression of infection into sepsis, severe sepsis, or septic shock. It is possible to use PCT to measure the activity of the infection-associated systemic inflammatory response, to control success of antibacterial therapy, and to estimate prognosis (Assicot et al. 1993. Lancet 341:515-8; Clec'h C et al. 2004. Crit Care Med 32:1166-9; Lee et al. 2004;. Yonsei Med J 45:29-37; Meisner et al. 2005. Curr Opin Crit Care 11:473-480; Wunder et al. 2004. Inflamm Res 53: 158-163). The increase of PCT levels in patients with sepsis correlates with mortality (Oberhoffrer et al. 1999. Clin Chem Lab Med 37:363-368).
During bacterial infections, plasma PCT concentrations are typically above 0.25 ng/mL. Recently, it has been found that in several non-infectious diseases, like coronary artery disease or acute coronary syndromes, PCT concentrations can be elevated above the normal range but below the concentrations, which have been known so far to be associated with bacterial infections requiring antibacterial treatment, and that these PCT concentrations are associated with a prognosis of adverse events in these patients (Sinnig et al. 2011. Circ J 75:1184-1191; Kelly et al. 2010. Biomarkers 15:325-331).
Patent applications EP 07015271.5 and EP 09719129.0 disclose the use of PCT in the risk stratification of patients suffering from stable coronary artery disease (CAD) and acute coronary syndromes (ACS), respectively.
Heart failure (HF), also termed congestive heart failure (CHF) is a cardiac condition that occurs when a problem with the structure or function of the heart impairs its ability to supply sufficient blood flow to meet the body's needs. It can cause a large variety of symptoms, particularly shortness of breath (SOB) at rest or during exertion and/or fatigue, signs of fluid retention such as pulmonary congestion or ankle swelling, and objective evidence of an abnormality of the structure or function of the heart at rest. However, some patients can be completely symptom free and asymptomatic structural or functional abnormalities of the heart are considered as precursors of symptomatic heart failure and are associated with high mortality (Wang et al. 2003. Circulation 108: 977-82). Heart failure is a common disease: more than 2% of the U.S. population, or almost 5 million people, are affected and 30 to 40% of patients die from heart failure within 1 year after receiving the diagnosis (McMurray J. J., Pfeffer M. A. 2005. Lancet 365: 1877-89). Heart failure is often undiagnosed due to a lack of a universally agreed definition and challenges in definitive diagnosis, particularly in the early stage. With appropriate therapy, heart failure can be managed in the majority of patients, but it is a potentially life threatening condition, and progressive disease is associated with an overall annual mortality rate of 10%. It is the leading cause of hospitalization in people older than 65 years (Haldemann G. A. et al. 1999. Am Heart J 137: 352-60). As a consequence, the management of heart failure consumes 1-2% of total health-care expenditure in European countries (Berry et al. 2001. Eur J Heart Fail 3: 749-53).
Chronic heart failure (chronic HF) is a long-term condition developing over months and years with a usually stable treated symptomatology. This condition is associated with the heart undergoing adaptive responses which, however, can be deleterious in the long-term and lead to a worsening condition. Acute heart failure (AHF) is a term used to describe exacerbated or decompensated heart failure, referring to episodes in which a patient can be characterized as having a change in heart failure signs and symptoms resulting in a need for urgent therapy or hospitalization. AHF develops rapidly during hours or days and can be immediately life threatening because the heart does not have time to undergo compensatory adaptations. Chronic HF may also decompensate which most commonly result from an intercurrent illness (such as pneumonia), myocardial infarction, arrhythmias, uncontrolled hypertension, or a patient's failure to maintain a fluid restriction, diet or medication.
Miller et al. examined in a cohort of patients with chronic HF hospitalized for decompensation of HF, the use of PCT for an intermediate-term prognosis of post-hospital cardiovascular mortality (mean follow-up 10 months) (Miller et al 2009. J Cardiovasc Trans Res 2:526-535). However, procalcitonin levels were not different between non-survivors and survivors. In contrast, PCT levels tended to be higher in survivors than in non-survivors. Maisel et al. reported that the level of PCT was significantly associated with the prognosis of short-term (90-days) all-cause mortality in patients diagnosed with acute heart failure (Maisel et al. 2012. Eur J Heart Fail, 14:278-286).
A method for the diagnosis of infections of the airways and lungs with associated heart failure is described in EP 07817601.3.
However, it is unknown whether relatively elevated PCT concentrations in patients with stable chronic heart failure or patients suspected of having stable chronic heart failure can be associated with the prognosis of an adverse event (e.g. mortality). The possibility of predicting adverse events at presentation of the patient is important, since early recognition of risk is a prerequisite for initiating measures helping to prevent the development of adverse events.
It has thus been the task of the present invention to investigate whether PCT levels in patients with stable chronic heart failure or patients suspected of having stable chronic heart failure are associated with the prognosis of adverse events (e.g. mortality).